Exploratory Investigation of Brain MRI Lesions According to Whole Sample and Visual Function Subtyping in Children With Cerebral Visual Impairment

BACKGROUND: There is limited research on brain lesions in children with cerebral visual impairment (CVI) of heterogeneous etiologies and according to associated subtyping and vision dysfunctions. This study was part of a larger project establishing data-driven subtypes of childhood CVI according to visual dysfunctions. Currently there is no consensus in relation to assessment, diagnosis and classification of CVI and more information about brain lesions may be of potential diagnostic value. Aim: This study aimed to investigate overall patterns of brain lesions and associations with level of visual dysfunction and to compare the patterns between the classification subgroups in children with CVI. METHODS: School-aged children with CVI received ophthalmological and neuro-psychological/developmental assessments to establish CVI-related subtyping. Other pediatric information was collected from medical records. MRI scans were coded according to a semi-quantitative template including brain regions (right hemisphere, left hemisphere, visual pathways) and summed for total scores. Non-parametric analyses were conducted. RESULTS: 28 children had clinical brain MRI scans available [44% of total sample, Group A (lower severity of visual dysfunctions) n = 16, Group B (higher severity) n = 12]. Total brain scores ranged between 0 and 18 (Group A mdn = 7, IQR = 0.8–10.0, Group B mdn = 10, IQR = 6.5–11.8) and were widespread across regions. 71 per cent had post-geniculate visual pathway damage. The median total brain and hemisphere scores of Group B were higher than subgroup A but differences did not reach statistical significance. No statistically significant associations were found between brain scores and vision variables (acuity, contrast sensitivity). CONCLUSION: This study found a spread of lesions across all regions on the brain scans in children with congenital CVI. The majority had damage in the postgeniculate visual pathways and visual cortex region suggesting this is an area of interest and potentially informative for diagnosis. However the subtyping classification did not show differences in number or region of lesions though the trend was higher toward Group B. This study confirms the complex diffuse and variable nature of brain lesions in children with congenital CVI, many of whom have other neurological impairments

Acute cervical longitudinally extensive transverse myelitis in a child with Lipopolysaccharide-Responsive-Beige-Like-Anchor-Protein (LRBA) deficiency: a new complication of a rare disease

Lipopolysaccharide responsive beige-like anchor protein (LRBA) deficiency is a primary immunodeficiency disorder (PID) that can cause a common variable immunodeficiency (CVID)-like disease. The typical features of the disease are autoimmunity, chronic diarrhea, and hypogammaglobulinemia. Neurological complications are also reported in patients affected by LRBA deficiency. We describe a 7-year old female with an acute cervical longitudinally extensive transverse myelitis (LETM) as a feature of LRBA deficiency. This is the first case of LETM associated with LRBA deficiency described in literature

CDKL5 deficiency disorder: progressive brain atrophy may be part of the syndrome

The clinical phenotype of Cyclin-Dependent Kinase-Like 5 (CDKL5) deficiency disorder (CDD) has been delineated but neuroimaging features have not been systematically analyzed. We studied brain magnetic resonance imaging (MRI) scans in a cohort of CDD patients and reviewed age at seizure onset, seizure semiology, head circumference. Thirty-five brain MRI from 22 unrelated patients were included. The median age at study entry was 13.4 years. In 14/22 patients (85.7%), MRI in the first year of life was unremarkable in all but two. In 11/22, we performed MRI after 24 months of age (range 2.5-23 years). In 8 out of 11 (72.7%), MRI showed supratentorial atrophy and in six cerebellar atrophy. Quantitative analysis detected volumetric reduction of the whole brain (-17.7%, P-value = 0.014), including both white matter (-25.7%, P-value = 0.005) and cortical gray matter (-9.1%, P-value = 0.098), with a reduction of surface area (-18.0%, P-value = 0.032), mainly involving the temporal regions, correlated with the head circumference (& rho; = 0.79, P-value = 0.109). Both the qualitative structural assessment and the quantitative analysis detected brain volume reduction involving the gray and white matter. These neuroimaging findings may be related to either progressive changes due to CDD pathogenesis, or to the extreme severity of epilepsy, or both. Larger prospective studies are needed to clarify the bases for the structural changes we observed

Teaching NeuroImages: radiologic features of septo-optic dysplasia plus syndrome

[no abstract available

Brain malformations associated to Aldh7a1 gene mutations: Report of a novel homozygous mutation and literature review

Background: The ALDH7A1 gene is known to be responsible for autosomal recessive pyridoxine-dependent epilepsy (OMIM 266100). The phenotypic spectrum of ALDH7A1 mutations is very heterogeneous ranging from refractory epilepsy and neurodevelopmental delay, to multisystem neonatal disorder. Aim: The present study aims at describing the phenotype associated with a novel homozygous ALDH7A1 mutation and the spectrum of brain malformations associated with pyridoxine-dependent epilepsy. Methods: We conducted a literature review on the Internet database Pubmed (up to November 2017) searching for ALDH7A1 mutations associated with brain malformations and brain MRI findings. Results: We present the case of two siblings, children of related parents. The proband presented neonatal focal seizures not responding to conventional antiepileptic drugs. Electroencephalography showed a suppression burst pattern and several multifocal ictal patterns, responsive to pyridoxine. Brain MRI was normal. Molecular analysis by targeted next-generation sequencing panel for epileptic encephalopathy disclosed a homozygous missense mutation of ALDH7A1. The same mutation was then found in a stored sample of DNA from peripheral blood of an older sister dead 3 years earlier. This girl presented a complex brain malformation diagnosed with a foetal MRI and had neonatal refractory seizures with suppression burst pattern. She died at 6 months of age. Literature review: The brain abnormalities most frequently reported in pyridoxine-dependent epilepsy include: agenesia/hypoplasia of the corpus callosum, not specific white matter abnormalities, large cisterna magna, ventriculomegaly, haemorrhages, cerebellum hypoplasia/dysplasia, and, more rarely, dysplasia of the brainstem and hydrocephalus. Discussion and conclusions: ALDH7A1 mutations have been associated to different brain abnormalities, documented by MRI only in few cases. The study cases expand the clinical spectrum of ALDH7A1 associated conditions, suggesting to look for ALDH7A1 mutations not only in classical phenotypes but also in patients with brain malformations, mainly if there is a response to a pyridoxine trial

Moyamoya syndrome and 6p chromosome rearrangements: Expanding evidences of a new association

Background: Moyamoya syndrome represents an etiologically heterogeneous cerebral evolutive angiopathy. It can be associated with both well-characterized and recently described genetic conditions with mendelian inheritance. Case report: We report the case of a moyamoya angiopathy in a prematurely born girl affected by congenital heart defect, mild facial dysmorphism, mild neurodevelopmental delay and borderline cognitive profile, associated to a de novo complex rearrangement involving the terminal segment of the short arm of chromosome 6. Conclusion: To the best of our knowledge, this is the second case described of pediatric moyamoya syndrome associated with a 6p complex rearrangement. Adding this case to the pertinent literature, we discuss the pathogenic role of rearrangements in 6p region in moyamoya syndrome and suggest to investigate in this region potential genes involved in angiogenesis or vascular homeostasis. (C) 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved

Temporal bone and intracranial abnormalities in syndromic causes of hearing loss: an updated guide.

To describe in detail the temporal bone and brain findings in both common and rare syndromic causes of hearing loss, with the purpose of broadening among radiologists and enhance the current understanding of distinct imaging features in paediatric patients with syndromic hearing loss. A detailed search of electronic databases has been conducted, including PubMed, Ovid Medline, Scopus, Cochrane Library, Google Scholar, National Institute for Health and Care Excellence (NICE), Embase, and PsycINFO. Syndromic causes of hearing loss are characterised by different and sometimes specific abnormalities in the temporal bone. A complete knowledge of the image findings in the temporal bones, brain, skull and other body regions is critical for the optimal assessment and management of these patients